Five storylines of differentiation
The transformation of an actively dividing basal cell into a dead scale proceeds simultaneously in five directions:
- Keratin accumulation: the number of keratin tonofibrils steadily increases until they fill the entire internal volume.
- Envelope formation: a special protein, keratolinin, is synthesized beneath the plasmalemma, thickening the wall of the scale about 20-fold.
- Lipid synthesis: lipids (ceramides and cholesterol sulfate) are produced in specific organelles (keratinosomes) to create a hydrophobic intercellular barrier.
- Organelle reduction: at later stages, the nucleus and all cytoplasmic organelles are completely degraded.
- Shape change: round or cuboidal cells gradually flatten, turning into 14-sided prisms.
Cytomorphological changes across layers
The morphology of keratinocytes changes as they progress from the basement membrane to the surface.
1. Basal layer (Stratum basale) The regeneration zone. This is where resting stem cells, transient keratinocytes (with active mitoses), and maturing cells reside. The shape is cuboidal or oval, with a large nucleus. The cytoplasm is intensely basophilic due to an abundance of ribosomes, where the synthesis of keratin tonofilaments begins. These filaments assemble into bundles and weave into desmosomes (connections to neighbors) and hemidesmosomes (connections to the basement membrane, which consists of lamina lucida and lamina densa).
2. Spinous layer (Stratum spinosum) The layer of mechanical strength (from 3–4 rows in thin skin to 10+ in thick skin). Cells acquire a polygonal shape with short processes ("spines") where desmosomes are located. Mitoses almost disappear. Tonofibrils are arranged concentrically around the nucleus to protect it. Lamellar granules (keratinosomes) appear, initiating lipid synthesis.
3. Granular layer (Stratum granulosum) The preparation phase for the final stage (3–4 rows of highly flattened cells). The breakdown of organelles begins. The synthesis of the protein filaggrin is triggered, which aggregates tonofibrils, forming visible basophilic keratohyalin granules. Concurrently, keratinosomes release lipids into the intercellular space, creating a waterproof barrier (analogous to pulmonary surfactant).
4. Clear layer (Stratum lucidum) Transitional zone (3–4 rows). Organelles are completely destroyed by lysosomal enzymes. Filaggrin uniformly permeates the cytoplasm (granularity disappears). The layer appears as a continuous luminous band due to an optical effect: the refractive indices of the intracellular matrix and intercellular lipids match, obscuring cell boundaries.
5. Cornified layer (Stratum corneum) Consists of dead flat prisms (corneocytes). Thickness ranges from 3 rows to 20 (on palms and soles). The scale is enclosed in a robust shell of cross-linked keratolinin, filled with insoluble "soft keratin" and air bubbles. Filaggrin loses its function here.
Mechanism of desquamation (shedding)
Cornified scales are held together by an intercellular lipid cement, in which cholesterol sulfate plays a key role. For physiological renewal of the epidermis, this "glue" must be dissolved.
In the superficial layers, the enzyme steroid sulfatase (released from Langerhans cell lysosomes) hydrolyzes cholesterol sulfate. Adhesion weakens, and the scales detach. In the genetic deficiency of this enzyme, shedding is blocked, leading to excessive thickening of the cornified layer—a pathology known as ichthyosis.
Features of hard keratin
Unlike the soft keratin of the skin (which is soluble in acids and alkalis), hard keratin is formed in hair and nails. Cornification here occurs rapidly, bypassing the stage of keratohyalin granules (direct transition). Hardness and chemical resistance are ensured by a high content of the amino acid cysteine and an abundance of strong disulfide cross-links. In the hair root, cornified scales are organized into two structures:
- Cortex: long scales positioned perpendicularly to the axis (like a fan), containing pigment and air.
- Cuticle: short scales arranged like roof tiles (6–10 layers, edges directed upwards).
Briefly: answers to topical questions
What other cell populations, besides keratinocytes, are part of the skin epidermis?
In addition to the main cell type (keratinocytes), the skin epidermis includes accompanying cell populations comprising immigrants and specialized cells.
- Melanocytes are pigment cells of neural crest origin located strictly in the basal layer.
- Intraepidermal macrophages (Langerhans cells) and interacting T-lymphocytes provide immune defense functions.
- Tactile cells (Merkel cells) are responsible for receptor function and the perception of light touch.
- Greenstein cells are also present within the heterogeneous cell population of the epidermis.
What layers (laminae) are distinguished in the ultramicroscopic structure of the epidermal basement membrane?
Two layers are distinguished in the basement membrane at the dermal-epidermal junction:
- Lamina lucida (lamina lucida).
- Lamina densa (lamina densa).
What types of collagen are part of the basement membrane and ensure its connection with the dermis?
The cited sources indicate that type IV and V collagens are associated with basement membranes.
Data regarding which specific structures or collagen types provide the direct connection between the epidermal basement membrane and the dermis are absent in the sources.
What structural layers does the hair root consist of?
In transverse cross-section, the hair root consists of three structural layers formed as a result of the differentiation of hair bulb cells.
- Cuticle (cuticula) — the outer thin layer consisting of short scales with a shingle-like arrangement.
- Cortex (cortex) — the main layer of the hair, formed by elongated cornified scales.
- Medulla (medulla) — the innermost layer of the central part of the hair, present only in long and guard hairs (absent in vellus hairs).
Epidermal cells are like people: in the basal layer they actively divide (youth), in the spinous layer they acquire desmosomal connections (maturity), in the granular layer they lose their nuclear individuality (old age), and in the cornified layer they turn into a flat monument to themselves.
Class and exam questions
Why is the stratum lucidum called that and why does it appear transparent?
In this layer, the light refractive indices of intracellular proteins and intercellular lipids completely coincide. As a result, the boundaries between individual cells visually blur, creating the effect of a homogeneous shiny band.
What are keratinosomes and what is their function?
These are special organelles (lamellar bodies) that appear in the spinous layer. They synthesize specific lipids (ceramides, cholesterol sulfate) which are then secreted to the exterior and glue the cornified scales together, forming a waterproof barrier.
What is the difference between hard and soft keratin?
Soft keratin is formed in the skin epidermis and is soluble in acids/alkalis. Hard keratin (in hair and nails) is resistant to chemicals due to a high cysteine content and numerous strong disulfide bonds.
What else to study on this topic
- Molecular composition and functions of keratolinin in the cornified envelope
- The role of filaggrin in the formation of keratohyalin granules
- Organization of intercellular lipids and the skin barrier function
- Architectonics of hair cornified scales: cuticle and cortex
- Pathogenesis of retention hyperkeratosis (ichthyosis)
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